There are a number of reports of a higher incidence of infectious disease, autoimmune disease, and malignancies in patients experiencing stressful events. There is also evidence association stress with the progression of HIV-1 infection. However, the research investigating the effect of stress on immune function has not adequately determined the immune alterations induced by stress, and has not used well-defined stressors. Our plan is to use Lewis rats in an aversive-conditioning paradigm in which we have documented pronounced and highly reproducible immune alterations. This approach affords a sensitive methodology for the assessment of the effect of psychological stress on immune function. The first aim is to make extensive in-vitro and in-vivo evaluations of the immunomodulatory effects induced by a conditioned aversive stimulus. The immunologic assessments will include the : (1) mitogenic response to plant lectins, (2) activity of natural killer cells, (3) production of interleukin-1 and interleukin-2, (4) quantification of lymphocyte subsets using flow cytometry, (5) in-vivo response to sheep erythrocytes, and (6) development of an experimentally induced immunologic disease, i.e., adjuvant-induced arthritis. For all assays, different compartments of the immune system, i.e., blood, spleen, and lymph nodes, will be evaluated. The second aim is to evaluate select forms of conditioning which differ in their modes of operation and functional properties, so as to assess the generality of the observed immune alterations. The additional forms will include: (1) contextual conditioning, (2) higher-order conditioning, and (3) inhibitory conditioning. The final aim is to evaluate the effect of immune activation on the conditioning process itself, so as to determine the underlying mechanisms and/or points of interaction between the conditioning process and the immune system. The significance of the research is viewed not only as providing important information about stress-induced alterations of immune function and health, but also as enhancing our knowledge of the conditioning and immune processes per se.